Abstract
Lung cancer is the leading cause of cancer-associated mortality worldwide. Despite the development of novel molecular therapies, the prognosis for patients with locally advanced or metastatic lung cancer remains poor. Therefore, the identification of novel therapeutic approaches is required. In numerous types of cancer, the constitutive activation of signal transducer and activator of transcription 3 (STAT3) signaling serves as a potent therapeutic target. The present study aimed to characterize the suppressive role of LLL12, a STAT3 small molecule inhibitor, in lung cancer cell proliferation and tumor growth. The mechanism of STAT3 signaling modulation by LLL12 was also investigated. The antitumor activity of LLL12 was revealed to take place via inhibition of lung cancer cell proliferation and migration in vitro. High and low doses of LLL12 significantly reduced tumor volume and weight in xenograft mice compared with that in the control group. Furthermore, LLL12 was demonstrated to reduce the level of STAT3 phosphorylation. These results suggested that LLL12 inhibited the proliferation and migration of A549 cells, and the increase in tumor volume in nude mice with lung cancer. This may be associated with the inhibitory effect of STAT3 phosphorylation and the expression of STAT3. The results of the present study suggest that constitutive STAT3 signaling is required for lung cancer cell survival and migration, and tumor growth in vivo. It is also indicated that LLL12 has clinical potential as a novel targeted therapy.